Neuropilin 1 regulates bone marrow vascular regeneration and hematopoietic reconstitution
| Autor: | Yurun Zhang, Tiancheng Fang, Vivian Y. Chang, Martina Roos, Lia Signaevskaia, Heather A. Himburg, Paulina K. Lin, Amara Pang, Mindy M. Kim, Joshua P. Sasine, Christina M. Termini, Orel Tabibi, Avradip Chatterjee, Michelle Li, Ramachandran Murali, John P. Chute, Nicollette J Setiawan |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Science General Physics and Astronomy Apoptosis Bone Marrow Cells General Biochemistry Genetics and Molecular Biology Article Stress signalling Mice Bone Marrow Neuropilin 1 medicine Animals Regeneration Multidisciplinary Chemistry Regeneration (biology) Haematopoietic stem cells Wnt signaling pathway Hematopoietic stem cell Cyclin-Dependent Kinase 5 Semaphorin-3A General Chemistry Hematopoietic Stem Cells Cardiovascular biology Neuropilin-1 Cell biology Stem-cell research Endothelial stem cell Mice Inbred C57BL Wnt Proteins Haematopoiesis medicine.anatomical_structure Female Bone marrow Stem cell Transcriptome Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) |
| ISSN: | 2041-1723 |
| Popis: | Ionizing radiation and chemotherapy deplete hematopoietic stem cells and damage the vascular niche wherein hematopoietic stem cells reside. Hematopoietic stem cell regeneration requires signaling from an intact bone marrow (BM) vascular niche, but the mechanisms that control BM vascular niche regeneration are poorly understood. We report that BM vascular endothelial cells secrete semaphorin 3 A (SEMA3A) in response to myeloablation and SEMA3A induces p53 – mediated apoptosis in BM endothelial cells via signaling through its receptor, Neuropilin 1 (NRP1), and activation of cyclin dependent kinase 5. Endothelial cell – specific deletion of Nrp1 or Sema3a or administration of anti-NRP1 antibody suppresses BM endothelial cell apoptosis, accelerates BM vascular regeneration and concordantly drives hematopoietic reconstitution in irradiated mice. In response to NRP1 inhibition, BM endothelial cells increase expression and secretion of the Wnt signal amplifying protein, R spondin 2. Systemic administration of anti - R spondin 2 blocks HSC regeneration and hematopoietic reconstitution which otherwise occurrs in response to NRP1 inhibition. SEMA3A – NRP1 signaling promotes BM vascular regression following myelosuppression and therapeutic blockade of SEMA3A – NRP1 signaling in BM endothelial cells accelerates vascular and hematopoietic regeneration in vivo. Ionizing radiation and chemotherapy deplete haematopoietic stem cells and damage the vascular niche. Here the authors show that irradiation induces SEMA3A secretion from bone marrow endothelial cells (ECs), inducing EC apoptosis via NRP1 and that NRP1 inhibition promotes vascular regeneration and R spondin 2 dependent hematopoietic regeneration. |
| Databáze: | OpenAIRE |
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